This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bredel, M. Articles by Sikic, B. I. Search for Related Content PubMed PubMed Citation Articles by Bredel, M. Articles by Sikic, B. I.

High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors

¹ Division of Oncology, Center for Clinical Sciences Research; and Departments of ² Neurosurgery, ³ Pathology, and ⁴ Neurology, Stanford University School of Medicine, Stanford, California and ⁵ Department of General Neurosurgery, Neurocenter, University of Freiburg, Freiburg, Germany

Requests for reprints: Markus Bredel, Division of Oncology, Stanford University School of Medicine, 269 Campus Drive, CCSR-1120, Stanford, CA 94305-5151. Phone: 650-498-6949; E-mail: mbredel{at}stanford.edu.

High-resolution genome-wide mapping of exact boundaries of chromosomal alterations should facilitate the localization and identification of genes involved in gliomagenesis and may characterize genetic subgroups of glial brain tumors. We have done such mapping using cDNA microarray-based comparative genomic hybridization technology to profile copy number alterations across 42,000 mapped human cDNA clones, in a series of 54 gliomas of varying histogenesis and tumor grade. This gene-by-gene approach permitted the precise sizing of critical amplicons and deletions and the detection of multiple new genetic aberrations. It has also revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations was shown predominantly associated with either astrocytic or oligodendrocytic tumor phenotype. Finally, five novel minimally deleted regions were identified in a subset of tumors, containing putative candidate tumor suppressor genes (TOPORS, FANCG, RAD51, TP53BP1, and BIK) that could have a role in gliomagenesis.

This article has been cited by other articles:

				H.-Q. Qu, K. Jacob, S. Fatet, B. Ge, D. Barnett, O. Delattre, D. Faury, A. Montpetit, L. Solomon, P. Hauser, et al. Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas Neuro Oncology, October 15, 2009; (2009) nop001v1. [Abstract] [Full Text] [PDF]

				M. Bredel, D. M. Scholtens, G. R. Harsh, C. Bredel, J. P. Chandler, J. J. Renfrow, A. K. Yadav, H. Vogel, A. C. Scheck, R. Tibshirani, et al. A Network Model of a Cooperative Genetic Landscape in Brain Tumors JAMA, July 15, 2009; 302(3): 261 - 275. [Abstract] [Full Text] [PDF]

				L.-y. Wang, A. Abyzov, J. O. Korbel, M. Snyder, and M. Gerstein MSB: A mean-shift-based approach for the analysis of structural variation in the genome Genome Res., January 1, 2009; 19(1): 106 - 117. [Abstract] [Full Text] [PDF]

				C. Erdman and J. W. Emerson A fast Bayesian change point analysis for the segmentation of microarray data Bioinformatics, October 1, 2008; 24(19): 2143 - 2148. [Abstract] [Full Text] [PDF]

				T. L. Lai, H. Xing, and N. Zhang Stochastic segmentation models for array-based comparative genomic hybridization data analysis Biostat., April 1, 2008; 9(2): 290 - 307. [Abstract] [Full Text] [PDF]

				B. Guan, P. Pungaliya, X. Li, C. Uquillas, L. N. Mutton, E. H. Rubin, and C. J. Bieberich Ubiquitination by TOPORS Regulates the Prostate Tumor Suppressor NKX3.1 J. Biol. Chem., February 22, 2008; 283(8): 4834 - 4840. [Abstract] [Full Text] [PDF]

				R. Tibshirani and P. Wang Spatial smoothing and hot spot detection for CGH data using the fused lasso Biostat., January 1, 2008; 9(1): 18 - 29. [Abstract] [Full Text] [PDF]

				A. Li, J. Walling, Y. Kotliarov, A. Center, M. E. Steed, S. J. Ahn, M. Rosenblum, T. Mikkelsen, J. C. Zenklusen, and H. A. Fine Genomic Changes and Gene Expression Profiles Reveal That Established Glioma Cell Lines Are Poorly Representative of Primary Human Gliomas Mol. Cancer Res., January 1, 2008; 6(1): 21 - 30. [Abstract] [Full Text] [PDF]

				I. B. Jeffery, S. F. Madden, P. A. McGettigan, G. Perriere, A. C. Culhane, and D. G. Higgins Integrating transcription factor binding site information with gene expression datasets Bioinformatics, February 1, 2007; 23(3): 298 - 305. [Abstract] [Full Text] [PDF]

				F. Liu, P. J. Park, W. Lai, E. Maher, A. Chakravarti, L. Durso, X. Jiang, Y. Yu, A. Brosius, M. Thomas, et al. A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma Cancer Res., November 15, 2006; 66(22): 10815 - 10823. [Abstract] [Full Text] [PDF]

				X. Yu, J. Lin, D. J. Zack, and J. Qian Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues Nucleic Acids Res., October 18, 2006; 34(17): 4925 - 4936. [Abstract] [Full Text] [PDF]

				P. L. Rosa, E. Viara, P. Hupe, G. Pierron, S. Liva, P. Neuvial, I. Brito, S. Lair, N. Servant, N. Robine, et al. VAMP: Visualization and analysis of array-CGH, transcriptome and other molecular profiles Bioinformatics, September 1, 2006; 22(17): 2066 - 2073. [Abstract] [Full Text] [PDF]

				T.-Y. Kim, S. Zhong, C. R. Fields, J. H. Kim, and K. D. Robertson Epigenomic profiling reveals novel and frequent targets of aberrant DNA methylation-mediated silencing in malignant glioma. Cancer Res., August 1, 2006; 66(15): 7490 - 7501. [Abstract] [Full Text] [PDF]

				M. Bredel, C. Bredel, D. Juric, G. R. Harsh, H. Vogel, L. D. Recht, and B. I. Sikic Functional Network Analysis Reveals Extended Gliomagenesis Pathway Maps and Three Novel MYC-Interacting Genes in Human Gliomas Cancer Res., October 1, 2005; 65(19): 8679 - 8689. [Abstract] [Full Text] [PDF]

				W. R. Lai, M. D. Johnson, R. Kucherlapati, and P. J. Park Comparative analysis of algorithms for identifying amplifications and deletions in array CGH data Bioinformatics, October 1, 2005; 21(19): 3763 - 3770. [Abstract] [Full Text] [PDF]